Background On May 8, 2018, the China National Medical Products Administration (NMPA) approved anlotinib, an orally administered anti-angiogenesis inhibitor, for the treatment of patients with advanced non-small cell lung cancer (NSCLC) who have progressed after treatment with two or more lines of prior systemic chemotherapy. Main body of the abstract China NMPA reviewed and inspected a regional double-blinded, placebo-controlled, Phase III trial comparing the overall survival (OS) of NSCLC patients between the anlotinib and placebo arms. A total of 437 patients were randomized (2:1) to receive either anlotinib ( n = 294) or placebo ( n = 143) once daily on a 2-week on and 1-week off schedule. Patients with epidermal growth factor receptor ( EGFR ) or activating anaplastic lymphoma kinase ( ALK ) genomic tumor aberrations should have disease progression on NMPA-approved therapy. Anlotinib is the first NMPA-approved drug for patients with advanced NSCLC who have progressed on at least two lines of prior systemic chemotherapies in China. The approval was based on a statistically and clinically significant improvement in median OS with anlotinib (9.46 months) compared with placebo [6.37 months; hazard ratio (HR]) = 0.70, 95% confidence interval (CI) = 0.55–0.89; two-sided log-rank P = 0.002]. The confirmed objective response rate (ORR) was 9.2% in the anlotinib arm and 0.7% in the placebo arm. The median duration of response (DoR) was 4.83 months, with a 95% CI of 3.31–6.97 months. The toxicity profile of anlotinib was consistent with that of known anti-angiogenesis inhibitors. Common adverse drug reactions (ADRs) in anlotinib-treated patients included hypertension (67.4%), hand–foot syndrome (43.9%), hemoptysis (14.0%), thyroid stimulating hormone (TSH) elevation (46.6%), and corrected QT interval (QTc) prolongation (26.2%). Short conclusion Anlotinib demonstrated a clinically significant OS prolongation as a novel therapeutic option for advanced or metastatic NSCLC following at least two lines of chemotherapy.

BackgroundAcute lymphoblastic leukemia (ALL) is the most frequently-occurring malignant neoplasm in children, but the pathogenesis of the disease remains unclear. In a microarray assay using samples from 100 children with ALL, SFRS1 was found to be up-regulated. Serine/arginine-rich splicing factor 1 (SRSF1, also termed SF2/ASF), encoded by the SFRS1 gene, had been shown to be a pro-oncoprotein. Our previous study indicated that SRSF1 can be methylated by protein arginine methyltransferase 1 (PRMT1) in vitro; however, the biological function of SRSF1 and PRMT1 in pediatric ALL are presently unknown.MethodsMatched, newly diagnosed (ND), complete remission (CR) and relapse (RE) bone marrow samples from 57 patients were collected in order to evaluate the expression patterns of SRSF1 and PRMT1. The potential oncogenic mechanism of SRSF1 and PRMT1 in leukemogenesis was also investigated.ResultsWe identified significant up-regulation of SRSF1 and PRMT1 in the ND samples. Importantly, the expression of SRSF1 and PRMT1 returned to normal levels after CR, but rebounded in the RE samples. Our observation that SRSF1 could predict disease relapse was of particular interest, although the expression patterns of SRSF1 and PRMT1 were independent of the cytogenetic subtypes. In pre-B-cell lines, both SRSF1 and PRMT1 expression could be efficiently attenuated by the clinical chemotherapy agents arabinoside cytosine (Ara-c) or vincristine (VCR). Moreover, SRSF1 and PRMT1 were associated with each other in leukemia cells in vivo. Knock-down of SRSF1 resulted in an increase in early apoptosis, which could be further induced by chemotherapeutics.ConclusionsOur results indicate that SRSF1 serves as an anti-apoptotic factor and potentially contributes to leukemogenesis in pediatric ALL patients by cooperating with PRMT1.

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Nanomaterials that respond to specific tumor microenvironments (TMEs), such as weakly acidic, hypoxia, and high glutathione (GSH), have shown promise in killing cancer cells with low toxicity and high specificity. Herein, a multistimulus TME-responding nanoplatform, composed of MCMnH and CaO2 nanoparticles, was prepared based on the exploration of the new characteristics of melanin nanoparticles (MNPs), which was found to promote photosensitizers to produce reactive oxygen species (ROS) under NIR irradiation. The MCMnH + CaO2 nanoplatform showed excellent performance of alleviating tumor hypoxia and amplifying the ROS reaction through the dual channels of MnO2 and CaO2, thus improving the combined antitumor effect of chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT). Furthermore, the MCMnH + CaO2 nanoplatform also demonstrated the capability of multimethod imaging, such as magnetic resonance imaging (MRI) and fluorescence imaging, which provided multiple schemes for the monitoring of the tumor treatment process. In conclusion, safe and efficient treatment and monitoring were achieved through the versatile and green antitumor nanoplatform in this article. Our study shows a good demonstration of an image-guided tumor microenvironment-responsive nanoplatform in the multimodal strategy toward cancer therapy.

Abstract. In this short note, we present a refinement of the well-known arithmetic-geometric mean inequality. As application of our result, we obtain an operator inequality.Mathematics subject classification (2010): 46A73, 26D07, 26D15.

Species distribution models are widely used in conservation biology and invasive biology. MaxEnt models are the most widely used models among the existing modeling tools. In the MaxEnt modeling process, the default parameters are used most often to build the model. However, these models tend to be overfit. Aiming at this problem, this study uses an optimized MaxEnt model to analyze the impact of past, present and future climate on the distributions of Codonopsis pilosula, an economic species, to provide a theoretical basis for its introduction and cultivation. Based on 264 distribution records and eight environmental variables, the potential distribution areas of C. pilosula in the last interglacial, middle Holocene and current periods and 2050 and 2070 were simulated. Combined with the percentage contribution, permutation importance, and jackknife test, the environmental factors affecting the suitable distribution area of this species were discussed. The results show that the parameters of the optimal model are: the regularization multiplier is 1.5, and the feature combination is LQHP (linear, quadratic, hinge, product). The main temperature factors affecting the distribution of C. pilosula are the annual mean temperature, mean diurnal range, and isothermality. The main precipitation factors are the precipitation seasonality, precipitation in the wettest quarter, and precipitation in the driest quarter, among which the annual average temperature contributes the most to the distribution area of this species. With climate warming, the suitable area of C. pilosula exhibits a northward expansion trend. It is estimated that in 2070, the suitable area of this species will expand to its maximum, reaching 2.5108 million square kilometers. The highly suitable areas of C. pilosula are mainly in Sichuan, Gansu, Shaanxi, Shanxi, and Henan Provinces. Our findings can be used to provide theoretical support related to avoiding the blind introduction of C. pilosula.

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The purpose of this note is to study impulsive control and synchronization of memristor based chaotic circuits shown by Muthuswamy. We first establish a less conservative sufficient condition for the stability of memristor based chaotic circuits. After that, we discuss the effect of errors on stability. Meanwhile, we also discuss impulsive synchronization of two memristor based chaotic systems. Our results are more general and more applicable than the ones shown by Yang, Li, and Huang. Finally, several numerical examples are given to show the effectiveness of our methods.